The aim of this proposal is to study and compare the factors regulating catecholamine formation and release in various regions of the central nervous system. We will investigate these factors in rat brain synaptosomal preparations isolated from predominantly dopaminergic areas (striatum, olfactory tubercle and nucleus accumbens) and predominantly noradrenergic areas (hypothalamus, hippocampus and cerebellum). The effects of depolarizing agents, such as potassium and veratridine, of phenylethylamine compounds, such as amphetamine and tyramine, and of divalent chelators such as EGTA will be studied in order to characterize regulatory properties in the various brain areas and to test the hypothesis that generalizable differences in regulation may exist between noradrenergic as compared to dopaminergic terminals in the central nervous system. Predictions of drug action based on the in vitro synaptosomal studies will be tested by monitoring the effects of drug administration on catecholamine formation in vivo in the various brain regions. These studies, in the areas of psychopharmacology and neuropharmacology, should further our understanding of psychoactive drug action and aid in the elucidation of the biochemical aspects of mental health and psychiatric disorders.